Sporadic four-repeat tauopathy with frontotemporal lobar degeneration, Parkinsonism, and motor neuron disease: a distinct clinicopathological and biochemical disease entity

Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism an...

Full description

Saved in:
Bibliographic Details
Published in:Acta neuropathologica 2010-07, Vol.120 (1), p.21-32
Main Authors: Fu, Yong-Juan, Nishihira, Yasushi, Kuroda, Shigetoshi, Toyoshima, Yasuko, Ishihara, Tomohiko, Shinozaki, Makoto, Miyashita, Akinori, Piao, Yue-Shan, Tan, Chun-Feng, Tani, Takashi, Koike, Ryoko, Iwanaga, Keisuke, Tsujihata, Mitsuhiro, Onodera, Osamu, Kuwano, Ryozo, Nishizawa, Masatoyo, Kakita, Akiyoshi, Ikeuchi, Takeshi, Takahashi, Hitoshi
Format: Article
Language:English
Subjects:
Adult
Aged
Astrocytes - metabolism
Astrocytes - pathology
Astrocytes - ultrastructure
Brain - metabolism
Brain - pathology
Brain - ultrastructure
Cytoplasm - metabolism
Cytoplasm - pathology
Cytoplasm - ultrastructure
Frontotemporal Lobar Degeneration - complications
Frontotemporal Lobar Degeneration - metabolism
Frontotemporal Lobar Degeneration - pathology
Humans
Japan
Male
Medicine
Medicine & Public Health
Middle Aged
Motor Neuron Disease - complications
Motor Neuron Disease - metabolism
Motor Neuron Disease - pathology
Neurofibrillary Tangles - metabolism
Neurofibrillary Tangles - pathology
Neurofibrillary Tangles - ultrastructure
Neuroglia - metabolism
Neuroglia - pathology
Neuroglia - ultrastructure
Neurons - metabolism
Neurons - pathology
Neurons - ultrastructure
Neurosciences
Original Paper
Parkinsonian Disorders - complications
Parkinsonian Disorders - metabolism
Parkinsonian Disorders - pathology
Pathology
Spinal Cord - metabolism
Spinal Cord - pathology
Spinal Cord - ultrastructure
tau Proteins - genetics
tau Proteins - metabolism
Tauopathies - complications
Tauopathies - metabolism
Tauopathies - pathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tau is the pathological protein in several neurodegenerative disorders classified as frontotemporal lobar degeneration (FTLD), including corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). We report an unusual tauopathy in three Japanese patients presenting with Parkinsonism and motor neuron disease (neuroimaging revealed frontotemporal cerebral atrophy in two patients who were examined). At autopsy, all cases showed FTLD with the most severe neuronal loss and gliosis evident in the premotor and precentral gyri. Although less severe, such changes were also observed in other brain regions, including the basal ganglia and substantia nigra. In the spinal cord, loss of anterior horn cells and degeneration of the corticospinal tract were evident. In addition, the affected regions exhibited neuronal cytoplasmic inclusions resembling neurofibrillary tangles. Immunostaining using antibodies against hyperphosphorylated tau and 4-repeat tau revealed widespread occurrence of neuronal and glial cytoplasmic inclusions in the central nervous system; the astrocytic tau lesions were unique, and different in morphology from astrocytic plaques in CBD, or tufted astrocytes in PSP. However, immunoblotting of frozen brain samples available in two cases revealed predominantly 4R tau, with the approximately 37-kDa and 33-kDa low-molecular mass tau fragments characteristic of CBD and PSP, respectively. No mutations were found in the tau gene in either of the two cases. Based on these clinicopathological, biochemical, and genetic findings, we consider that the present three patients form a distinct 4R tauopathy associated with sporadic FTLD.
ISSN:0001-6322
1432-0533
DOI:10.1007/s00401-010-0649-2